Method and system for mammalian joint resurfacing

ABSTRACT

A method and system for the creation or modification of the wear surface of orthopedic joints, involving the preparation and use of one or more partially or fully preformed and procured components, adapted for insertion and placement into the body and at the joint site. In a preferred embodiment, component(s) can be partially cured and generally formed ex vivo and further and further formed in vivo at the joint site to enhance conformance and improve long term performance. In another embodiment, a preformed balloon or composite material can be inserted into the joint site and filled with a flowable biomaterial in situ to conform to the joint site. In yet another embodiment, the preformed component(s) can be fully cured and formed ex vivo and optionally further fitted and secured at the joint site. Preformed components can be sufficiently pliant to permit insertion through a minimally invasive portal, yet resilient enough to substantially assume, or tend towards, the desired form in vivo with additional forming there as needed.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation-in-part of US applicationfiled Apr. 12, 2002 and assigned U.S. Ser. No. 10/121,455, which is acontinuation-in-part of US application filed Mar. 15, 2002 and assignedU.S. Ser. No. 10/098,601, which is a continuation of an internationalpatent application filed Aug. 28, 2001 and assigned Ser. No.PCT/US01/41908 which itself claims the benefit of Provisional U.S.Application Ser. No. 60/228,444, filed Aug. 28, 2000, the entiredisclosures of which are incorporated herein by reference.

TECHNICAL FIELD

In one aspect, this invention relates to biomaterials formed ex vivo forimplantation and use within the body. In another aspect, the inventionrelates to in situ curable biomaterials. In yet another aspect, thisinvention further relates to the field of orthopedic implants andprostheses, and more particularly, for implantable materials for use inorthopedic joints.

BACKGROUND OF THE INVENTION

Applicant has previously described, inter alia, prosthetic implantsformed of biomaterials that can be delivered and finally cured in situ,e.g., using minimally invasive techniques. See for instance, U.S. Pat.Nos. 5,556,429, 5,795,353, 5,888,220, 6,079,868, 6,140,452, 6,224,630and 6,248,131 as well as published International Application Nos. WO95/30388 and WO 97/26847 and International Application PCT/US97/20874filed Nov. 14, 1997 (the disclosures of each of which are incorporatedherein by reference). Certain of these applications describe, interalia, the formation of a prosthetic nucleus within an intervertebraldisc by a method that includes, for instance, the steps of inserting acollapsed mold apparatus (which in a preferred embodiment is describedas a “balloon”) through a cannula that is itself positioned through anopening within the annulus, and filling the balloon with a flowablebiomaterial that is adapted to finally cure in situ and provide apermanent disc replacement. See also, Applicant's “Porous Biomaterialand Biopolymer Resurfacing System” (PCT/US99/10004), as well as“Implantable Tissue Repair Device (PCT/US99/11740), and “Static Mixer”(PCT/US99/04407) applications.

See also, U.S. Pat. No. 3,030,951 (Mandarino), U.S. Pat. No. 4,203,444(Bonnell et al.), U.S. Pat. No. 4,456,745 (Rajan), U.S. Pat. No.4,463,141 (Robinson), U.S. Pat. No. 4,476,293 (Robinson), U.S. Pat. No.4,477,604 (Oechsle, III), U.S. Pat. No. 4,647,643 (Zdrahala), U.S. Pat.No. 4,651,736 (Sanders), U.S. Pat. No. 4,722,948 (Sanderson), U.S. Pat.No. 4,743,632 (Marinovic et al.), U.S. Pat. No. 4,772,287 (Ray et al.),U.S. Pat. No. 4,808,691 (König et al.), U.S. Pat. No. 4,880,610(Constanz), U.S. Pat. No. 4,873,308 (Coury et al.), U.S. Pat. No.4,969,888 (Scholten et al.), U.S. Pat. No. 5,007,940 (Berg), U.S. Pat.No. 5,067,964 (Richmond et al.), U.S. Pat. No. 5,082,803 (Sumita), U.S.Pat. No. 5,108,404 (Scholten et al.), U.S. Pat. No. 5,109,077 (Wick),U.S. Pat. No. 5,143,942 (Brown), U.S. Pat. No. 5,166,115 (Brown), U.S.Pat. No. 5,254,662 (Szycher et al.), U.S. Pat. No. 5,278,201 (Dunn etal.), U.S. Pat. No. 5,525,418 (Hashimoto et al.), U.S. Pat. No.5,624,463 (Stone et al.), U.S. Pat. No. 6,206,927 (Fell), and EP 0 353936 (Cedar Surgical), EP 0 505 634 A1 (Kyocera Corporation), EP 0 521573 (Industrial Res.), and FR 2 639 823 (Garcia), WO 93/11723 (RegenCorporation), WO 9531946 (Milner), WO 9531948 (Kuslich).

Applicant's PCT Application No. PCT/US97/00457 (WO 9726847A1) includesthe optional use of a mold, such as a balloon, and describes the mannerin which “[t]he mold created within the joint is preferably ofsufficient shape and dimensions to allow the resulting cured biomaterialto replace or mimic the structure and function of the removedfibrocartilage. The mold can be formed of synthetic and/or naturalmaterials, including those that are provided exogenously and thoseprovided by the remaining natural tissues. The mold can either beremoved from the site, upon curing of the biomaterial, or issufficiently biocompatible to allow it to remain in position.”

Applicant's later PCT Application No. PCT/US97/20874 (WO 9820939A2)further describes the manner in which “‘mold’ will refer to the portionor portions of an apparatus of the invention used to receive, constrain,shape and/or retain a flowable biomaterial in the course of deliveringand curing the biomaterial in situ. A mold may include or rely uponnatural tissues (such as the annular shell of an intervertebral disc)for at least a portion of its structure, conformation or function. Themold, in turn, is responsible, at least in part, for determining theposition and final dimensions of the cured prosthetic implant. As such,its dimensions and other physical characteristics can be predeterminedto provide an optimal combination of such properties as the ability tobe delivered to a site using minimally invasive means, filled withbiomaterial, and optionally, then remain in place as or at the interfacebetween cured biomaterial and natural tissue. In a particularlypreferred embodiment the mold material can itself become integral to thebody of the cured biomaterial.”

Applicant's own use of such mold apparatuses to date has concentratedlargely on the use of thin, extensible balloons adapted to be positionedand then filled in situ with curable biomaterial, with particular use asa replacement for the intervertebral disc following microdiscetomy. Inturn, there has been considerably less focus, to date, on the use of anysuch molds in other joints, such as the knee. FIGS. 6 and 7 ofApplicant's PCT Publication No. WO 920939 A2, for instance, shows aballoon and corresponding drilling template for use in knee surgery, theballoon having foot portions protruding from a generally ovoidinflatable portion.

Finally, U.S. Pat. No. 6,206,927 describes a self-centering meniscalprosthesis device suitable for minimally invasive, surgical implantationinto the cavity between a femoral condyle and the corresponding tibialplateau is composed of a hard, high modulus material shaped such thatthe contour of the device and the natural articulation of the kneeexerts a restoring force on the free-floating device. In what appears tobe a related manner, Sulzer has introduced a unicompartmentalinterpositional spacer to treat osteoarthritis in the knee. See “LittleDevice Could Pack a Big Punch”, Sulzer Medica Journal Edition 2/2000(www.sulzermedica.com/media/smj-full-tex/2000/0002-full-text-6.html).The device is described as a metallic kidney-shaped insert which fillsin for the damaged cartilage between the femur and the tibia.

Such a metallic device, as described in either the Fell patent and/orSulzer's product literature, is described as appropriate for use inyounger patients with moderate to severe chondromalacia, particularlysince the product provides a hard, self-centering meniscal device thatis “devoid of physical means that fix its location”. In so doing, thedevice of Fell et al. tends to require a significant amount of intactcartilage and meniscus. Applicant's own products to date, includingthose improved embodiments described herein, have been largely gearedtoward more elderly patients, where such healthy cartilage is lacking.In turn, Applicant's devices tend to provide angular correction andimproved anchoring of the implant at the joint surface.

The recently issued Search Report in parent application PCT/US01/41908includes two references, namely DE 19823325C1 and DE 4339895 C1 directedto multipart devices that include portions mechanically affixed to bone,and in turn, are unrelated to a polymeric interpositional device of thetype presently claimed.

In spite of developments to date, there remains a need for a jointprosthesis system that provides an optimal combination of propertiessuch as ease of preparation and use, and performance within the body.

BRIEF DESCRIPTION OF THE DRAWING

In the Drawing:

FIG. 1 shows top and side perspectives (FIGS. 1a and 1 b, respectively)of a preferred preformed knee implant prepared according to the presentinvention.

FIG. 2 shows an embodiment, including an in situ view 2 a and a raisedperspective view 2 b, in which preformed components adapted to beinserted and assembled in situ.

FIG. 3 shows an alternative embodiment in which preformed components areemployed, shown as disassembled components.

FIGS. 4 and 5 show an embodiment in which a substantially open(saucer-shaped) mold is inserted into the joint site, to be filled witha corresponding curable biomaterial in situ, including side and bottomperspective views 4 a and 4 b, respectively, and views showing the moldbeing positioned (5 a) and being filled while imposition upon the knee(5 b).

FIG. 6 shows a variety of alternative embodiments 6 a, 6 b, 6 c and 6 d,respectively, that include one or more preformed component.

FIG. 7 shows a variety of alternative means 7 a, 7 b, 7 c, and 7 d,respectively for anchoring a preformed component such as that shown inFIG. 6d.

FIG. 8 shows a further variety for anchoring or stabilizing a preformedportion by the use of ancillary portions and/or surface texture, namelyembodiments shown as FIGS. 8a, 8 b, and 8 c.

FIG. 9 shows a variety of embodiments, namely those shown as FIGS. 9a, 9b, and 9 c, in a substantially closed (balloon like) mold is adapted tobe inserted into the joint site and filled with a corresponding curablebiomaterial.

FIG. 10 shows a mold adapted for use as an acetabular mold in connectionwith the replacement of the articulating surface in a hip.

FIG. 11 shows a patella femoral joint form suitable for use incombination with the method and system of this invention, includingraised perspective view 11 a, top view 11 b, side view 11 c, and a sideview 11 d of the farm in position upon a condyle.

FIGS. 12 and 13 show various views of a particularly preferred kneeimplant of the present invention, including top plan view 12 a, frontplan view 12 b, side plan view 12 c, section view 12 d across A—A, andsection view 12 e across C—C, as well as top plan views of implants 13 aand 13 b for the left and right knees, respectively.

SUMMARY OF THE INVENTION

The present invention provides a method and system for the creation ormodification of the wear surface of orthopedic joints, including one orboth of two articulating surfaces and/or portions thereof, andparticularly articulating joints such as the knee. In one preferredembodiment, the method relies, at least in part, upon the manner inwhich the various stages of curing a curable biomaterial, and in turn,the various stages of forming a component from the cured or curingbiomaterial, can be correlated and optimized in a desired manner. Inturn, such a method provides the ability to both generally andspecifically form the component for use in situ.

The present invention includes a variety of embodiments, each of whichpreferably includes one or more components that are formed ex vivo, andthat are adapted to be inserted and finally formed or assembled in situin order to provide a final prosthesis and articulating joint surface.Examples of the various embodiments include, for instance,

1) one or more components that are each at least partially, andoptionally completely, molded ex vivo, in a manner that permits thecomponent to be inserted, and optionally finally formed, in situ,

2) a plurality of preformed components adapted to be assembled in situ,for instance in an overlapping or interlocking fashion,

3) an insertable open (e.g., saucer shaped) mold, adapted to be insertedand positioned within the joint site, and there used in combination witha flowable biomaterial adapted to be delivered to the open mold in situ,under conditions that permit the flowable biomaterial to cure in contactand/or combination with the mold in order to form a final prosthesis,

4) one or more generally extensible envelope (e.g., balloon-type) molds,adapted to be positioned and filled in situ with corresponding curablebiomaterials, one or more of the molds themselves providing one or moreregions of generally non-extensible, preformed material. In oneembodiment, for instance, a plurality of such envelope portions (e.g., abi-compartmental single envelope) can be adapted for use on both themedial and lateral tibial surfaces, respectively.

By the selection and use of a suitable biomaterial, and other featuresas described herein, the present invention provides an optimalcombination of benefits, as compared to methods previously described.Such benefits include those that arise in the course of preparation andstorage (e.g., sterility, storage stability), those that arise in thesurgical field itself (e.g., ease of use, adaptability, predictability),and those that arise in the course of long term use within the body(e.g., biocompatibility, moisture cure characteristics, tissue congruityand conformability, retention, wear characteristics, andphysical-mechanical properties).

In one preferred embodiment, the method and system involve thepreparation and use of partially or completely cured components that canbe formed outside the body, for insertion and placement into the body,and that can then be further formed within the joint site in order toenhance conformance. The optional ability to finally form one or morecomponents in situ provides various additional benefits, such asincreased control over the overall size and shape of the finalprosthesis, improved shape and compliance of the surface apposingnatural bone, and finally, improved shape and compliance of theopposite, articulating surface. The method and system permit the on sitepreparation or previous manufacture of a unicompartmentalinterpositional arthroplasty device from polymeric materials such aspolyurethane.

In a related and particularly preferred embodiment, the implant can beprepared (including full cured) ex vivo, for later implantation. In aparticularly preferred embodiment, as described below, the presentinvention therefore provides an implant that is designed to be formed toand congruent with the tibial surface, having a final femoral surfaceshape that serves largely as a glide path with respect to the femoralcondyle. Such a device can be used in patients having joints that haveprogressed to the stage of “bone on bone”, and thus provides areplacement for the function of articular cartilage as well as meniscus,and particularly at the central weight-bearing area, in order to restorealignment, providing an elastomeric, cushioning function. A preferredimplant of this type is also congruent with the tibial surface, basedupon both its initial shape, together with whatever final shaping mayoccur in situ. In turn, the present implant is more permanently anchoredin place, in significant part by one or more posterior projections, suchas the posterior lip shown in FIGS. 1, and 12-13 as well by the optionalbut preferred use of anterior fixation means (such as embedded sutures).

As shown in those Figures, such an embodiment includes a uniquecombination of a femoral glide path and convexity of the tibial surfaceof the implant, together with a posterior mesial lip. In turn, asprovided in the Figures and related description, the implant provides anindentation adapted to accommodate the tibial spine, which together witha slight feathering of the implant on the underside at the tibial spine,the general kidney shape of the implant, and the convexity of the tibialsurface, will permit the implant to be congruent with the concave tibiaand the posterior mesial lip that extends over the posterior portion ofthe tibia and into the mesial side of the tibia into the PCL fossa ofthe tibia. Importantly, such an implant can be provided in various sizesto accommodate different anterior-posterior dimensions of the tibia anddifferent tibial concavities. In other words, the amount of convexity ofthe tibial surface will be varied with the different sizes depending onthe amount of actual concavity that there is in the tibia.

As used herein, the word “cure”, and inflections thereof, will refer tothe extent to which a curable biomaterial, as used to form a componentof this invention, has begun or completed whatever physical-chemicalreactions may be contemplated in the course of fully forming thecomponent, prior to or at the surgical site, for long term use in situ.In turn, the biomaterial can be considered as uncured (as in componentparts that have not yet been mixed or compositions that have not yetbeen activated), or it can be partially cured (e.g., wherein thecomponents have been mixed, or compositions activated, under conditionssuitable to begin the curing process), or it can be fully cured (e.g.,in which case, whatever chemical reactions may have occurred havesubstantially subsided). Generally, uncured compositions are sterile,storage stable, and often flowable, though are typically not yet formedor capable of being formed.

Curing compositions, by contrast, generally begin as flowablecompositions, but become nonflowable over a finite time period as theybegin to gel or set. Curing compositions can also be minimally formed,e.g., outside the body by the use of molds and/or suitable shapingtools, and/or within the body, as by the initial positioning of thecomponent on supporting bone and by the repositioning of opposing,articulating bone surfaces. Thereafter, it is contemplated and possiblethat some compositions of this invention can be further formed, overtime, as by the gradual effect of articulating bone in the course oflong term use.

As also used herein, the word “form”, and inflections and variationsthereof, will refer to the manner and extent to which a component hasbeen sized and shaped, in either a general and/or specific manner, foruse at a joint site. In turn, the forming of such a component can occureither ex vivo and/or in vivo, as well as in a general manner (e.g., bythe use of an ex vivo mold or tools) and/or a specific manner (e.g., byfinal curing in apposition to supporting bone and/or opposingarticulating bone surfaces), as well as combinations thereof.

A component can be “specifically” formed in this manner in order toconform the component (and particularly its surfaces) to thecorresponding specific shapes and dimensions of bone in situ, includingboth supporting bone surfaces and/or opposing (e.g., articulating) bonesurfaces. Such specific conformation, in turn, can be used to improve avariety of characteristics of the final implant, including comfort,mechanical performance, and/or long term stability. Such conformationcan also include aspects in which one or more components, or thecomposite prosthesis, are “conformed” in correspondence with the jointsite (e.g., by final shaping and curing processes that occur in situ).

Such conformation can also include aspects in which the components, orprosthesis itself, are adapted to be “deformed” within the site, as bythe application of force. For instance, a substantially fully formedcomponent can be provided to have sufficient mechanical properties(e.g., strength and resilience) to permit it to be inserted into a jointsite and effectively deformed under normal anatomic forces For instance,a substantially convex component can be deformed to assume thecorresponding concave shape in situ, in, while retaining sufficientresilient strength to tend towards its original convex shape (e.g.,analogous to the manner in which a locking washer can be deformed inuse, while tending toward its original shape). Preferably, a final kneecomponent is adapted to be deformed under conditions of use within thebody (e.g., under physiologic load), while maintaining desired size andtibial congruency, and in a manner that provides desired fit andthickness for desired angular correction.

Hence a “preformed” component will generally refer to a component thatis at least partially formed ex vivo, as by the surgeon's selection anduse of an appropriately sized ex vivo mold. Such a preformed componentcan be specifically formed as well, including in an ex vivo fashion, asby the use of a customized mold that is itself reflective of theparticular dimensions and contours of the intended joint site. Suchcustomized molds can be prepared, for instance, by the use of externalimaging means, and/or by the appropriate use of negative and/or positivemolds taken at the tissue site. Optionally, and preferably, thepreformed component is specifically formed, in whole or in part, bybeing positioned in situ, prior to the completion of the curing process,and in apposition to both supporting bone and opposing bone surfaces.Once positioned within the joint site, any such component or prosthesiscan be adapted to be deformed in order to improve its retention and/orperformance in situ, e.g., resiliently deformed upon release ofdistracting forces and repositioning of the opposing bone surface.

For instance, a preformed composition is provided, formed initially bythe ex vivo onset of cure, in which the composition can be implantedwithin on the order of 10 seconds to several days of the onset of cure,preferably within about 30 seconds to about 10 minutes, and morepreferably within about one to about five minutes, while maintaining asurface exotherm of less than about 50C, and more preferably less thanabout 45C once positioned within the body.

Once positioned in vivo, optional preferred preformed components of thisinvention are adapted to be finally shaped, for a period of betweenabout 10 seconds and one or more hours, and more preferably betweenabout one minute and about five minutes. The lower limit is definedlargely by the time it takes to effectively reposition bone, orotherwise re-establish suitable force on the implant. The upper limit,in turn, is generally defined by the susceptibility of the implantedcomposition to further deformation or shaping. Such final shaping isgenerally accomplished, at least in part, under the force brought aboutby repositioning articulating bone surfaces. In one preferredembodiment, the partially cured composition is implanted underconditions that permit it to deform less than about 15%, preferably lessthan about 10%, and most preferably less than about 5%, underphysiologic forces, while maintaining tibial congruency and impartingdesired angular correction.

Hence, a particularly preferred preformed component of this inventioncan be implanted within an initial about one to about five minutes ofthe onset of its formation, and once implanted can be further molded orformed for a further period of about one to about five additionalminutes, in a manner that permits the resultant implant to substantiallyretain a desired final form and function.

The system of the present invention thereby provides the surgeon with avariety of options, based on the manner in which these curing andforming processes are correlated. In one particularly preferredembodiment, for instance, the surgeon is provided with a compositionadapted to be partially cured and generally formed ex vivo, and thenpromptly inserted into the body and positioned at the joint site, whereit can be finally, and specifically, formed in the course of becomingfully cured.

By partially or fully curing the prosthesis ex vivo, the present systemsimplifies the preparation process considerably, e.g., by lessening oravoiding potential problems (such as curing in the presence of moisture,and surface exotherm in the presence of tissue) that can arise when acomparable composition is mixed and delivered to the joint site while itis still flowable. Surprisingly, the present system permits suchprostheses to be not only formed, but also manipulated and inserted intothe joint (e.g., through an incision of between about 1 cm and about 3cm). Once inserted, the prosthesis can be positioned, and further formedin situ, all within a reasonable time frame. In fact, it has been foundthat the procedure is amenable to outpatient use and even regionalanesthesia.

Moreover, the present system can avoid the use of such processes as thedrilling anchor holes into the underlying bone, distraction of the kneejoint, ligament release, leveling of the tibial plateau, and the variousother procedures typically involved with delivering the biomaterialdirectly to the joint site in still flowable form. Yet, the prosthesisof the present invention provides a combination of properties such asthe extent of congruence with underlying bone, wear characteristics,fracture toughness, and avoidance of fibrillated articular cartilage,that meets or exceeds the combination of properties obtained using acomparable biomaterial in flowable form, delivered and largely cured insitu.

In addition to its immediate use in such joints as the knee, the systemof the present invention provides particular advantages when applied toball and socket joints, such as the hip. In one such embodiment, aballoon can be filled with a biomaterial as described herein, andinserted and positioned within the acetabulum, prior to or followingfilling, to provide a soft, conformable, durable lining for theplacement of a hip prosthetic portion. In a further embodiment, themethod and system involve the preparation and use of one or morepartially or fully cured component(s) formed outside the body, forinsertion and placement into the body and optionally further fitting andsecuring at the joint site. These preformed component(s) typicallyrequire less manipulation at the bedside and allow for alternativemethods of terminal sterilization, and final inspection and release atthe manufacturing site.

In a particularly preferred embodiment, the present invention thereforeprovides an implant that is designed to be formed to and congruent withthe tibial surface, having a final femoral surface shape that serveslargely as a glide path with respect to the femoral condyle.

This can be compared to other devices, such as that of the '927 patentdescribed above, which discloses a “self centering” device, formedentirely outside the body, and generally of a hard metal, by firstdetermining the geometry of the entire knee compartment, including boththe femoral and tibial surfaces. The device is designed to be very hard,and based on such things as the concavity and convexity of varioussurfaces, which are designed to permit continued movement (translationaland rotational) and re-positioning of the device within the kneecompartment in the course of use. In turn, the device is permitted andexpected to continually move within the joint over the course of itsuse.

The present device can be used in patients having joints that haveprogressed to the stage of “bone on bone”, and thus provides areplacement for the function of articular cartilage as well as meniscus,and particularly at the central weight-bearing area, in order to restorealignment. The implant provides an elastomeric, cushioning function, ascompared to the rigid and hard device of the '927 patent. The presentimplant is also congruent with the tibial surface, based upon both itsinitial shape and the final shaping that occurs in situ. In turn, thepresent implant is more permanently anchored in place, in significantpart by the posterior lip shown in FIGS. 1, and 12-13 as well by the useof anterior fixation means (such as embedded sutures).

Finally, the presently preferred implant has a peripheral thickness thatis generally thinner than the thickness of their central portion, and ispositioned only partially within the knee compartment as defined in the'927 patent, having a posterior lip that extends well beyond acompartment defined in that manner, and that serves a key role infixation.

DETAILED DESCRIPTION

The method and system (e.g., preformed component(s) and/or curablebiomaterial and mold) can be used to prepare a final prosthesis, invivo, that provides a first major surface in apposition to and retainedupon the supporting bone itself, and a second (generally substantiallyparallel and opposite) major surface adapted to provide a wear surfacefor opposing (e.g., articulating) bone. By “retained upon” it is meantthat the final prosthesis is maintained in a desired position upon thesupporting bone surface in a manner suitable for its intended use, e.g.,by the use of one or more anchor points, by the use of adhesive or othersuitable interface materials, by the use of sutures, staples, and thelike, and/or by a mechanical lock achieved by the combination of abone-contacting surface suitably conformed or conformable to the terrainof supporting bone, together with the retaining (and optionallyincluding deforming) effect achieved upon repositioning opposingarticulating bone surface.

The first and second major surfaces can be provided in any suitablemanner, for instance, 1) by the preparation and insertion of a singlepartially cured and generally preformed component into the joint,preferably under conditions that permit the component to become further,and specifically, formed in vivo, 2) by adding a flowable biomaterial toan initial preformed component (e.g., in the shape of a balloon or openmold) positioned at the tissue site, 3) by placing one or more fullycured and preformed components at the tissue site and optionally furtherfitting, adapting and/or securing the component(s) as needed, and/or 4)by assembling one or more preformed components in situ (e.g., side byside in an interlocking fashion upon the surface) such that theassembled components cooperate to provide the first and second majorsurfaces.

The system can therefore include modular implants, that include one ormore preformed components as described herein, in combination with oneor more other (e.g., metallic) components. Any or all of such componentscan be made using materials having “shape memory” that permits thecomponents to be easily inserted into the joint space, in a manner thatpermits the component(s) to assume or recover an alternative shape uponthe application of energy (e.g., heat slightly above body temperature).Optionally, such alternative shape can be achieved prior to insertioninto the body. Alternatively, the molded in the body implant can betaken out and reformed (e.g., by heat, radiation or other suitablemeans) and reimplanted for final fit.

In addition to the partially or fully cured preformed component(s)and/or curable biomaterial and related molds, the method and system ofthis invention include the optional use of various additional materialsand/or steps, e.g., to prepare the bone surface itself, to providesuitable interfaces (e.g., adhesive interfaces and/or protrusions thatcan be further secured to the joint site or by smoothing of the femoralcondyle or tibial plateau as needed), to treat one or more surfaces inorder to provide them with different or improved properties as comparedto the inherent properties of the material providing the surface, andthe like. Examples of such materials include, for instance, the use ofadhesive materials, tissue in-growth stimulators, and fibrous materials(e.g., webs adapted to tether the implant and/or to facilitate fibroustissue ingrowth).

The partially or fully cured preformed component(s) can themselves eachprovide uniform or non-uniform properties, and can be provided in aplurality or range of styles and sizes. These components can be designedto conform to lateral or medial compartments, or both, and to right orleft knees, or both. In a preferred embodiment, all embodiments can beinserted into the joint site in a minimally invasive fashion. By“minimally invasive”, in this context, it is meant that the procedure ofsizing, inserting, positioning and forming the prosthesis, in situ, canpreferably be accomplished without the need for open, invasive incisionsof the type conventionally used for inserting total knee prostheses. Ina preferred embodiment, the partially cured preformed components can befurther formed and fully cured in vivo to enhance compliance with thejoint site.

The surface of the partially or fully cured preformed component(s) canalso be modified to provide any desired properties (e.g., promoteadhesion), such as by the design and use of polymers themselves or bysurface treatment of the fully cured or curing embodiments to providesuitable reactive groups such as amines, hydroxyl groups, or otherreactive or hydrogen bonding functionalities. Similarly, the partiallycured preformed component or fully cured component, including balloonsor composite materials, can be provided with appropriate surfacecoatings, e.g., biologically active agents to promote desired tissueinteractions, including tissue or cellular adhesion, such as thoseselected from the group consisting of cytokines, hydroxyapatite,collagen, and combinations thereof. Such biologically active agents canalso include, for instance, anti-inflammatory agents, antitumor agents,antibiotics, complement inhibitors, cytokines, growth factors, orinhibitors of growth factors and cytokines, as well as combinations ofany such biologically active agents with each other and/or withadjuvants, and the like.

In one embodiment of this invention, partially cured, and generallypreformed components are inserted into the joint site, and there furtherand specifically formed to enhance compliance. In an alternativeembodiment, fully cured components in the shape of a balloon or openmold are employed to provide a final composite material by inserting theballoon or mold into the joint and there filling it with a biomaterialthat cures in situ and conforms with the joint site. In anotheralternative embodiment, the fully cured component(s) are provided andinserted into the joint either singly or piecemeal and optionallyfurther fitted and secured in vivo.

As an example of the first such embodiment, the invention provides anopen ex vivo mold, adapted to approximate the desired dimensions of thejoint site, and to receive a curable biomaterial. A suitable mold can beformed, for instance, from the use of conventional materials such assilicone materials, that permit the curing biomaterial component to beeasily and entirely removed at the desired time. Optionally, the moldcan itself be provided with a coating or release liner, including thosethat can be integrated, in whole or in part, with the component thusformed. Once the flowable biomaterial has been delivered and partiallycured in this ex vivo mold, and any optional molding or fabricatingsteps have occurred, the biomaterial can be removed from the mold andinserted into the joint site, under conditions suitable to permit it tobe further and finally formed in vivo to enhance conformance with thejoint site. Optionally, additional ex vivo forming steps or features canbe performed, e.g., by imparting desired curvature and femoral glidepaths, prior to inserting and final forming in vivo.

Also, in the course of molding the component ex vivo, and/ortransferring it to the tissue site, various structures and/or materialscan be incorporated into and/or onto the component itself, to enhanceits placement, retention and/or performance in situ. For instance, themold itself can be provided in a form sufficient to impart variousintegral structural features, such as tibial “tabs”, adapted to provideor improve the retention of the component at the tissue site. Such tabs,for instance, can be provided in the form of one or more protrusionsintegral with the mold itself and adapted to be positioned within and/oraffixed to the soft tissue and/or bone in vivo. Examples of such tabsare shown, for instance, in FIG. 1, where reference number 18 depicts araised posterior portion.

An insertable component can also be provided with one or more ancillaryportions or protrusions formed of materials other than that used to formthe bulk of the component itself. For instance, sutures or fibrousmaterials can be incorporated into or onto the bulk material, for use inimproving the initial and/or long term retention of the component insitu, e.g, by tethering the prosthesis at the joint site and in adesired position. Such other materials can be temporarily positionedinto or upon the mold itself, for instance, or otherwise provided, in amanner that permits them to become integrated into the biomaterial as itfills the mold and becomes partially cured ex vivo. With the resultingcomponent positioned in situ, the protrusions can be used to tether theimplant, by securing them to the surrounding soft tissue and/or bone byuse of adhesives, sutures, screws, pins, staples, or the like, and othertypes of anchors, or combinations thereof, which in turn can be preparedusing bioabsorbable and/or non-bioabsorbable cements, composites, andadhesives. The materials can provide both an immediate fixationfunction, and optionally also a desired long term function, bypermitting them to be either absorbed by the body over time, and/or topermit or encourage fibrous tissue ingrowth for long term fixation.

The reinforcing material can be provided in any suitable form, e.g., asfibers (e.g., sutures) or as a uniform woven or non-woven fabric,optionally including one or more reinforcing fibers or layers. Asuitable non-woven fabric, for instance, is preferably a material suchas is commercially available under the trade name Trevira Spunbond fromHoechst Celanese Corporation. The non-woven fabric is generally composedof continuous thermoplastic fiber, needle punched together to yield afelt-like fabric. In addition to fabrics like Trevira Spunbond, othermaterials such as polyester staple mat, glass fiber mat, as well asother organic and inorganic fiber mats and fabrics can be employed.

Reinforcing fibers can be included within the woven or non-woven fabric,or provided as separate layers of a composite. Such fiber layers canpreferably include a directional reinforcing fiber layer of organic orinorganic structural reinforcing fibers such as fiberglass, carbonfibers, aramid fibers which is available from DuPont Corporation underthe trade name Kevlar, linear polyethylene or polypropylene fibers suchas is commercially available from Allied-Signal, Inc. (now Honeywell)under the trade name Spectra, or polyester fibers. The phrase“reinforcing fiber” can include any fiber which, when used in its ownright or added to a composite fabric material, retains or enhancesdesired structural properties. The fibers can be randomly oriented, orpreferentially, they can be oriented in one or more directions. While anumber of specific types of materials have been given for use as thereinforcing fiber layer, it will be appreciated by those of ordinaryskill in the art that other equivalent-type reinforcing fiber layers canbe employed in the practice of the invention. A reinforcing fiber layercan be itself used to secure the prosthesis, or can be attached to awoven or non-woven fiber layer having a number of interstices or pores.Preferably, the reinforcing fiber layer and other fiber layers aresecured to each other mechanically, as by conventional stitching, needlepunching, stapling or buttons. In the case of certain applications,adhesives can also be used.

Similarly, a partially cured preformed component (and/or ancillaryportions incorporated therein) can also be provided with suitable meansto improve its ability to retain the component in situ, e.g., by the useof surface characteristics that provide improved chemical interactionswith the joint site. Such interactions can be achieved by the judicioususe of bulk material compositions themselves and/or the use of adhesivesor other suitable interface materials. The partially cured, preformed,component can also be physically modified to increase its interactionswith joint site, as by surface roughening, etching or cross-hatching,which would tend to provide increased surface area, and in turn,improved mechanical retention. A partially cured, preformed, componentcan also be retained by external means that are otherwise secured to thesurrounding bone and/or soft tissue by use of adhesives, sutures,screws, pins, staples or the like or combinations thereof. On the majorsurface opposing articulating bone, the partially cured preformedcomponent can be provided with suitable means as well, intended toimprove or alter either its compliance and/or interactions with theopposing bone surface.

In one particularly preferred embodiment, the system includes apartially cured preformed component that is first molded outside of thejoint site and adapted to be delivered to a tissue site and therepositioned in a fixed position. The mold can be of an open or closedconfiguration (and/or can involve a one- or multi-step molding process),adapted to preform one or both major surfaces, respectively. Oncepositioned, the partially cured component is adapted to be initially fitand positioned within the joint site, and to thereafter become betterconformed to the specific dimensions and/or terrain (e.g., anatomicstructure) of the joint site in vivo. Optionally, and preferably, themolds are designed to yield components that have optimum adhesion andconformance to the joint sites. The molds may also be heated during theex vivo partial curing process to optimize component properties or toprovide a component that is more formable in vivo.

In an alternative preferred embodiment, the method and system involvethe preparation and use of one or more fully or partially curedcomponent(s) formed outside the body, for insertion and placement intothe body and optionally further fitting and securing at the joint site.In one embodiment, the invention provides a single preformed componentthat is inserted into the joint site and optionally further fitted orsecured as needed. In another embodiment, the invention provides aplurality of preformed components, formed of the same or differentmaterials, and adapted to be delivered and positioned at the tissue sitein a manner that provides a final composite. The components can becombined at the site in any suitable fashion, e.g., by providing amechanical lock and/or by the use of interfacial materials such asadhesive layers. The components can be combined in any suitable fashion,e.g., as layers upon the bone, or as individual side-by-side componentsadapted to traverse the bone surface when combined. The use of preformedcomponent(s) can require less manipulation at the bedside and allow foralternative methods of terminal sterilization, and final inspection andrelease at the manufacturing site. The various means of retainingpartially cured preformed components, discussed herein, can be adaptedto work with fully cured preformed components.

The method and system of this invention can be used for repairing avariety of mammalian joints, including human joints selected from thegroup consisting of the tibial plateau of the knee, the acetabulum ofthe hip, the glenoid of the shoulder, the acromion process of theshoulder, the acromio-clavicular joint of the shoulder, the distaltibial surface of the ankle, the radial head of the elbow, the distalradius of the forearm, the proximal phalanx surface of the great toe,the proximal metacarpal surface of the thumb, and the trapezium of thewrist.

Those portions or combinations of preformed component(s) that contactthe bone surface are preferably adapted to physically conform closely tothe prepared bone surface, e.g., to its macroscopic physical contours.Such conformation can be provided or enhanced in any suitable manner,e.g., 1) by providing a partially cured preformed component that isfirst made in an ex vivo mold and then adapted or modified to conform tothe surface (e.g., by further forming in vivo), and/or 2) by use of apreformed balloon or composite mold material that is inserted into thejoint site and filled with a flowable biomaterial that cures in vivo sothat it conforms with the joint site and/or 3) by the use of fully curedpreformed component(s) that has optimum geometry for biomaterialcompliance once placed in the joint site and/or 4) by the preparationand use of a suitable (e.g., thin) interface material between bone andpreformed component (e.g., adhesive, filler, or cement material), and/or5) by the use of physical restraining means, such as adhesives, pins,staples screws, sutures or the like that are attached to protrusions inthe component itself or to an external means of securing it.

In yet other embodiments, the system of this invention can include theuse of materials or markers (e.g., radiopaque) positioned within or uponthe implant, to aid in visualization. e.g., using fluoroscopy or otherX-ray techniques.

The method and system of this invention will be further described withreference to the Drawing, wherein:

FIG. 1 shows a top and side perspective of a preferred preformed kneeimplant (10) prepared using an ex vivo mold according to the presentinvention. The implant provides a first major surface (12) adapted to bepositioned upon the tibial surface, and a generally planar second majorsurface (14) adapted to be positioned against the femoral condyle. In atypical embodiment, the second major surface, in turn, is preferablyprovided with a femoral glide path (16) to facilitate its performance insitu, in the form of a generally central (e.g., oval) depression about0.5 mm, or more preferably about 1 mm to about 5 mm deep at its lowestpoint (2 mm as shown) and about 20 mm, and more preferably about 30 mmto about 50 mm in length by 10 mm to 30 mm in width (40 mm by 20 mm asshown). Those skilled in the art, given the present description, willreadily determine the actual dimensions for optimal use, in bothabsolute and relative terms, depending on such factors as the actualjoint size and desired results (e.g., angular correction). As shown, theimplant is also provided with a tibial projection (18), adapted to catchthe posterior portion of the tibial plateau by extending over the rim ofthe tibial plateau distally. The body of the implant can have dimensionson the order of between about 35 mm, and preferably about 40 mm to about60 mm in the anterior-posterior dimension, between about 20 mm, andpreferably 30 mm to about 35 mm, or even about 40 mm in themedial-lateral dimension, and a maximum thickness (at the posterior lipof between about 8 mm, more preferably about 10 mm, and about 20 mm, orabout 2 mm to about 4 mm (e.g., 3 mm) greater than the thickness of theimplant at the center. As a result, it can be seen that fixation isaccomplished by effectively capping the tibial plateau with one or moreprojections extending distally over the rim of the plateau.

FIG. 2 shows an embodiments in which a plurality of preformed componentsare adapted to be inserted and assembled in situ to provide the finalimplant (20) FIG. 2a shows an embodiment, in which preformed components(22 through 25, respectively) are assembled in a side-by-side mannersequentially, and in situ, and upon the tibial surface. The matablepreformed sections each provide at least a portion of the resultantbone-contacting surface and wear surface, as well as one or moreportions adapted to provide a mechanical lock with one or morerespective other portions. The mechanical lock can be achieved in anysuitable manner, as by the provision of corresponding male and femaleportions, respectively. The portions can be mated, in situ, e.g., in apress fit or sliding manner, in order to attach the respectivecomponents. As can be seen in the raised perspective of the sameembodiment, and FIG. 2b, in the resultant assembly, the combinedcomponents cooperate to provide both a tibial bone-contacting surface(28) and a wear surface (26).

In the alternative embodiment of FIG. 3, rather than being positioned ina side-by-side fashion across the bone surface (as in FIG. 2), a finalimplant is provided using interlocking preformed components (show inthis case as portions 31 through 33, respectively) are instead providedin a form that permits them to be stacked upon each other, e.g., bylayering or sliding them onto each other, and positioned upon thesurface, in situ. The portions can be assembled in any suitable fashion,e.g., entirely on the tissue site, entirely ex vivo, or in varyingcombinations as desired. Optionally, and preferably, the generallyplanar portions are provided with corresponding matable portions, e.g.,in the form of grooves and tabs to provide a sliding fit, or adepression and corresponding projection to provide either a press fit,snap fit, or other suitable fit sufficient to prevent lateraldisplacement to the extent desired. The resultant formed prostheticimplant can be provided with various features as described herein,including desired molded portions adapted to provide better fit orperformance. Top portion (31) is particularly well suited to provide adesirable wear surface, while one or more intermediate portions (asshown by element 32) are adapted to provide an optimal combination ofsuch properties as thickness, cushioning, and angular correction. Asshown the lowermost portion (33) is shown with a projection (34) adaptedto be retained within a corresponding anchor hole or suitable depressionformed into the bone itself. FIGS. 3b and 3 c provide generally bottomand top views, respectively, showing the manner in which the portionscan be combined in a layered fashion.

In the embodiment of FIG. 3, preformed layers are shown havingprotrusions adapted to be positioned in a corresponding indentationwithin each underlying layer (or bone), in order to form a compactstack. In such an embodiment, the corresponding system will typicallyinclude at least two preformed components, including the initial,bone-contacting component, and final component providing the wearsurface. The system can provide one or more intermediate layers, e.g.,the number and/or selection of which can be used to provide a finaldesired height to the overall composite, and/or to provide differingproperties (e.g., with respect to compressibility, resilience, tissueingrowth), and/or to provide improved retention between the first andfinal components.

FIG. 4a shows an embodiment in which a substantially open(saucer-shaped) mold (40) is inserted into the joint site, to be filledwith a corresponding curable biomateral in situ. The top (42) of themold is open to receive biomaterial (not show), while the bottom (44)provides a lower major surface (46) adapted to contact bone andterminates in a filled protrusion (48) adapted to be positioned within acorresponding anchor point drilled in the bone itself. The anterior edge(50) of the cup is substantially perpendicular to the plane of the cupitself, while the posterior edge (52) is tapered (and optionally raised)to accommodate the corresponding shape of the tibial spine.

As shown, and for use in an adult human, the ex vivo mold accommodates apredetermined volume of biomaterial of on the order of about 5 ml toabout 15 ml. As a further advantage of this invention, the amount ofbiomaterial actually can be predetermined and controlled to correspondwith the ex vivo mold volume. In addition the ex vivo molds are designedfor optimum sizing and conformance to the joint site and MRI softwaremay be used to chose best mold for joint site. Implant thickness andhence angular correction can be controlled in this way.

FIG. 4b shows a bottom perspective view of the mold apparatus of FIG.4a, showing the filled protrusion (48). The posterior edge portion (andparticularly the posterior mesial edge portion, as seen in the figure)can be seen as provided with a groove or indentation (54), again toaccommodate the typical shape of the corresponding tibial spine.Overall, the mold can be seen as assuming a generally kidney-shapedconfiguration, adapted to correspond with the tibial surface. Such amold can be provided in a plurality of sizes, and shapes, to be selectedat the time of use to accommodate the particular patient's needs andsurgeon's desires.

FIGS. 5a and 5 b show the mold of FIG. 4a being positioned upon a tibialsurface (FIG. 5a), with the protrusion positioned within a correspondinganchor point, and (in FIG. 5b) with the tip of a biomaterial deliverycannula (56) positioned upon it, and with flowable biomaterial (58)being shown in the course of delivery.

FIG. 6 shows a variety of alternative embodiments that include one ormore preformed component. FIG. 6a shows a simple wedge shaped embodiment(60), in which the posterior portion (62) is significantly increased insize as compared to the anterior (64). FIG. 6b shows an implant (66)molded to provide portions (here, layers) having differing wearcharacteristics, including a preformed top having improved wear ascompared to the separately formed bottom portion (70). FIG. 6c, bycomparison, shows a plurality of components (72) adapted to bepositioned and assembled in situ at the time of surgery. These includean upper portion (74) having improved wear characteristics as comparedto the others, a bottom portion (78) being suitably formed to thepatient's geometry and desired angular correction, and one (or more)central portions (76) adapted to be positioned between the top andbottom portions to achieve desired properties such as overall thickness,angles, and/or physical chemical properties (such as moduli).

The embodiment of FIG. 6d shows a single piece (80) as might be cut frompreformed material at the time of surgery, while FIG. 7 shows a varietyof alternative means for anchoring a preformed component such as thatshown in FIG. 6d. These include the use of a grout (82) or othersuitable interface material as shown in FIG. 7a; the use of a separateexternal retaining device (84) as shown in FIG. 7b; the use ofexternally provided pins, screws, sutures, etc. as exemplified byelements (86) which generally traverse the body itself as in FIG. 7c;and the use of one or more anchor portions (88) positioned along one ormore suitable surfaces as shown in FIG. 7d.

FIG. 8 shows a further variety for anchoring or stabilizing a preformedportion by the use of ancillary portions and/or surface texture,including a roughened surface (90) as in FIG. 8a; or tabs (e.g.,provided by fabric or suture like materials) as shown as elements 92 and94 of FIGS. 8b and 8 c, respectively. The surface texture can include,for instance, a dimpled or other suitably textured surface to improvelubricity. In a preferred embodiment, the texture would be sufficient toallow entrapment of lubricant under no load or low loads, followed byobliteration of the pattern with load. In yet another alternativeembodiment, a femoral forming device of the type described inApplicant's previous U.S. Provisional Application Serial No. 0/341,070can be used to impart a textured surface. In practice, the preformedcomponents can benefit from any suitable combination of the variousfeatures and embodiments described or shown herein.

FIG. 9 shows a variety of embodiments in a substantially closed (balloonlike) mold is adapted to be inserted into the joint site and filled witha corresponding curable biomaterial, the mold itself providing apreformed articulating wear surface, including FIG. 9a which shows aninflatable balloon portion (96) that includes an integral preformed wearsurface and portion (98), as well as a lumen (100) adapted to fill theinflatable portion with flowable biomaterial. FIG. 9b shows acorresponding balloon (102) though without a preformed portion, andincluding its biomaterial lumen (104). Although not shown, the balloonof this or any embodiment can include various interior and/or exteriorsurface coatings, and can have regions and/or layers having differentdesired physical-chemical properties (such as porosity). FIG. 9c shows abi-compartmental closed balloon-like mold (106), wherein eachcompartment is adapted to conform to a respective medial or lateraltibial surface.

FIG. 10 shows a mold adapted for use as an acetabular mold (110) inconnection with the replacement of the articulating surface in a hip,when filled with biomaterial, the mold forming a concave portion adaptedto retain a corresponding femoral head. The mold is shown providing athin generally cup-shaped mold adapted to be filled in any suitable form(e.g., using a removable conduit (not shown) attached to the spacebetween inner and outer sealed layers (116 and 114, respectively)forming the mold.

FIG. 11 shows a patella-femoral joint form suitable for use incombination with the method and system of this invention. As shown inthe views of 11 a through 11 c, the form includes a silicone or othersuitable pad material (122) having aluminum or other suitable stayportions (124) and terminal handle or grasping portions (126). In use,with the knee at a generally 45 degree angle, the piece is formed to thefemoral bone surface, with its form maintained by bending the aluminumstays. With anchor points cut into the femoral bone, if desired, theform is held tight against the bone with the upper handle held away frombone to permit the delivery of curable biopolymer between the form andthe bone. As polymer is placed onto the bone (and into any anchorpoints) the form is maintained for a time sufficient to suitably formthe polymer, whereafter it can be removed.

FIG. 12 shows various views of a particularly preferred implant of thepresent invention, of the general type shown in FIG. 1 and describedabove, including a top plan view (a), front plan view (b), side planview (c), section view (d) taken along A—A of FIG. 12(a) and a sectionview (e) taken along C—C of FIG. 12(a). FIG. 13, in turn, show side byside top plan views (a) and (b) of corresponding implants for the leftand right knees, respectively. Reference numbers for the variousportions correspond to those described in FIG. 1, including preformedknee implant (10), the first major surface (12) adapted to be positionedupon the tibial surface, and a generally planar second major surface(14) adapted to be positioned against the femoral condyle. The secondmajor surface is shown having a femoral glide path surface (16) tofacilitate its performance in situ, adapted to form a generally centraldepression having the dimensions described herein. The glide path isfully formed in situ, by a suitable combination of both shaping andrepositioning of the femoral condyle in the manner described herein.

An implant of the type shown provides various benefits, including thecorrection of varus deformities, based in significant part upon thepresence and configuration of the posterior mesial lip (18), and thecutout (kidney bean shaped) for the intercondylar eminence (see FIG. 4b,ref 54). The tibial projection (18) is adapted to catch the posteriorportion of the tibial plateau. The implant itself has dimensions asprovided herein, and can be provided using one of a collection of moldsof multiple sizes and/or styles in accordance with the variousparameters of the present invention. A kit can be provided containingmolds of various sizes, e.g., varying by 1 mm or 2 mm increments inthickness and providing a range of anterior to posterior dimensions.Such molds can also be used to provide implants having bottoms ofvarious shapes, e.g., either a flat or curved bottom, and for either theleft or right knee.

An implant such as the configuration shown in FIG. 12 is preferably usedin a method that includes first determining the proper implant thicknessneeded to match physiological valgus. The surgeon prepares the sitearthroscopically, removing excess cartilage and removing the medialmeniscus to the medial ring, using a portal of about 1 cm in order toprovide suitable arthroscopic access while maintaining the presence offluid in the joint. The implant can be initially molded ex vivo, using amold selected from those available and including one or more embedded orattached fixation portions (e.g., anterior sutures or tabs), at whichtime it is inserted into the knee. The surgeon will then typically feelthe implant once in position, to confirm that the implant is properlyseated, and will extend the knee to provide varus stress on the lowerleg, obtaining congruency as the implant continues to cure by finallymolding both surfaces of the implant (to both the tibial surface andcondyle, respectively).

Optionally, and preferably, the surgeon can also use a femoral formingdevice (e.g., spoon-shaped device) of the type described in copending USProvisional Application mailed Dec. 7, 2001 and entitled “Method andDevice for Smoothing The Surface of Bone in an Articulating Joint”, thedisclosure of which is incorporated herein by reference, in order toprepare a femoral glide path and remove unwanted undulations. After asuitable time, e.g., about 1 to about 5 minutes, and typically at about2 minutes using presently preferred polyurethane compositions, theimplant can be sutured to the anterior rim, and the knee can be flexedto obtain complete range. Optionally, during or following thisprocedure, the joint can be filled with a suitable fluid and visualized,after which the knee is extended and braced, with the access portal(s)closed by suitable means (e.g., sutured).

As described in Applicant's co-pending U.S. provisional application No.60/228,444, the present application describes a method and system forthe creation or modification of the wear surface using an implantedmaterial fixed to the support structure of the original wear surface, togenerally conform to the shape of the original surface in a mammal. Amethod or system where the end of the bony surface is a rotating,sliding or rolling surface, such as in the knee, finger, hip, toe,spine, wrist, elbow, shoulder, ankle, or TMJ joint. The implant willfunction:

a) as a spacer,

b) as an impact absorber

c) as a surface with improved coefficient of friction (as compared tothe diseased surface), and/or

d) to increase the weight bearing area and improve congruency of thejoint surface (as compared to the diseased condition).

The method and system of this invention can be applied to areas ofaseptic necrosis, such as the nevecular bone in the wrist. The materialto be implanted consists of a plurality of materials, such as polymers,including polyurethane, polyethyelenes, polyureas, polyacrylates,polyurethane acrylates, hydrogels, epoxies and/or hybrids of any of theabove.

In an alternative embodiment, the surface can be provided by any of aseries of metals, including titanium, stainless steel, cobalt chromemillithium alloys and tantalum. Other surface materials can includevarious ceramics and biologic polymers.

The implantable material for the resurfacing can be formed ex vivoand/or in vivo as an injectable material that sets up to the moldedshape. The methods for changing state from liquid to solid state includecooling or heating, the passage of time, which allows for a change ofstate, or a chemical reaction between different reactants. The reactioncan be exothermic or endothermic. The set-up can be light activated orchemically catalyzed or it could be heat activated. Examples of suchsystems include flowable polymers of two or more components, lightactivated polymers, and polymers cured either by catalysts or by heat,including body heat, or any suitable combination thereof. Molds can beused in the form of balloons, dams or retainers. They can be used incombination with the local anatomy to produce the desired shape andgeometry. Molds can be of materials that are retained and becomes partof the implant or could be removed after curing of the biomaterialcomponent.

In an alternative embodiment, the material would be semi-solid and couldbe shaped and then set up in vivo. This would allow for the minimallyinvasive application, either through an arthroscopic portal or through asmall mini arthrotomy. As a further embodiment, the material could besynthesized ex vivo and then machined to fit using imaging topre-determine the desired geometry and size of the implant. As a furtheralternative, a range of implant sizes could be provided and sizing couldbe accomplished during the procedure. An ex vivo mold could be fit usingmolding materials and the implant could be molded on site just prior toimplantation.

Fixation methods for the implant would include biologic glues to gluethe implant to the underlying surface, trapping of the implant into acavity on the surface that causes a mechanical lock, using variousanchors to the underlying structure and fixing the implant to thatsurface or using mold retainers and/or screws, staples, sutures or pins.In alternative embodiment, anchors in the underlying structure may beused for fixing the implant to that surface and we may also use a tissueingrowth system to secure anchoring.

In the preferred embodiment, the patient will have a diagnosis ofosteoarthritis and have loss of cartilage on the articulating surface. Adetermination will be made of the amount of correction needed for thereestablishment of a normal angle of articulation. The ligaments will bebalanced so that there is no loss of range of motion with the implant inplace and the surface will be placed in such a position that theeventual resulting surface geometry reestablishes the same plane andorientation of the original articular surface.

Access to the site is obtained in a minimally invasive way. In apreferred embodiment, this is accomplished through arthroscopic meanswith arthroscopic portals. In an alternative embodiment, the access isaccomplished by a mini arthrotomy with a small incision that allowsaccess to the joint without sacrificing nerves, vessels, muscles orligaments surrounding the joint. In the preferred embodiment fibrillatedarticulating cartilage that is degenerated is removed down to thesubchondral surface. The surface is dried and prepared for appropriateanchoring. This may include anchor points that give a mechanical lock orthat alternatively simply supply horizontal and lateral stability. Thesurface may be prepared by drying and roughening in case a tissueadhesive is used. Pre-made anchors may be installed. These may be madeof various metallic materials or of polymers and may consist of pegsthat would extend up through the implant to anchor it to the underlyingsurface. This surrounding subchondral bone may be roughened to enhancetissue ingrowth or implant adhesion. The final geometry of the implantmay be determined by a dam or mold that is placed on the joint at thetime the material is implanted, when the implant is installed using anin situ cured technique (in the manner shown in FIGS. 1 and 4 ofApplicant's provisional parent application).

For pre-made material formed at the surgical site within a mold, variousforms of stabilization could be used, including anchor points ortitanium screws. Alternatively, the pre-made material could be made offsite to the specs developed from imaging of the patient's joint surface.In a third embodiment, multiple sizes could be made off site and theselection of the appropriate implant size could be chosen at the time ofsurgery. Two alternatives shown in FIG. 2 of the parent provisionalapplication include a single segment that can be installed through aportal or a series of segments that can be installed through a portaland locked together once inside the joint. They would be placedsequentially and then anchored to the bone by anchor points cut in thebone or by screws or tissue ingrowth. Finally, a robot, a jag or othercutting fixture could be used to prepare the bony surface for thepre-made implant to a fixed geometry of the anchor point.

Both the preformed component(s) and flowable biomaterial, if used, canbe prepared from any suitable material. Typically, the materials includepolymeric materials, having an optimal combination of such properties asbiocompatibility, physical strength and durability, and compatibilitywith other components (and/or biomaterials) used in the assembly of afinal composite. Examples of suitable materials for use in preparing thepreformed component(s) may be the same or different from the in situcuring biomaterial, and include polyurethanes, polyethylenes,polypropylenes, Dacrons, polyureas, hydrogels, metals, ceramics,epoxies, polysiloxanes, polyacrylates, as well as biopolymers, such ascollagen or collagen-based materials or the like and combinationsthereof.

Examples of suitable materials for use in preparing the flowablebiomaterial, if used, include polyurethanes, polyureas, hydrogels,epoxies, polysiloxanes, polyacrylates, and combinations thereof.

In a presently preferred embodiment, the preformed component(s) and theflowable biomaterial, if included, each comprise a biocompatiblepolyurethane. The same or different polyurethane formulations can beused to form both the preformed component(s), e.g., by an injectionmolding technique, as well as for the flowable biomaterial, if present.

Suitable polyurethanes for use as either the preformed component orbiomaterial can be prepared by combining: (1) a quasi-prepolymercomponent comprising the reaction product of one or more polyols, andone or more diisocyanates, and optionally, one or more hydrophobicadditives, and (2) a curative component comprising one or more polyols,one or more chain extenders, one or more catalysts, and optionally,other ingredients such as an antioxidant, and hydrophobic additive.

In the embodiment in which an in situ curing polymer is used, thepresent invention preferably provides a biomaterial in the form of acurable polyurethane composition comprising a plurality of parts capableof being mixed at the time of use in order to provide a flowablecomposition and initiate cure, the parts including: (1) aquasi-prepolymer component comprising the reaction product of one ormore polyols, and one or more diisocyanates, optionally, one or morehydrophobic additives, and (2) a curative component comprising one ormore polyols, one or more chain extenders, one or more catalysts, andoptionally, other ingredients such as an antioxidant, hydrophobicadditive and dye. Upon mixing, the composition is sufficiently flowableto permit it to be delivered to the body, and there be fully cured underphysiological conditions. Preferably, the component parts are themselvesflowable, or can be rendered flowable, in order to facilitate theirmixing and use.

The flowable biomaterial used in this invention preferably includespolyurethane prepolymer components that react either ex vivo or in situto form solid polyurethane (“PU”). The formed PU, in turn, includes bothhard and soft segments. The hard segments are typically comprised ofstiffer oligourethane units formed from diisocyanate and chain extender,while the soft segments are typically comprised of one or more flexiblepolyol units. These two types of segments will generally phase separateto form hard and soft segment domains, since they tend to beincompatible with one another. Those skilled in the relevant art, giventhe present teaching, will appreciate the manner in which the relativeamounts of the hard and soft segments in the formed polyurethane, aswell as the degree of phase segregation, can have a significant impacton the final physical and mechanical properties of the polymer. Thoseskilled in the art will, in turn, appreciate the manner in which suchpolymer compositions can be manipulated to produce cured and curingpolymers with desired combination of properties within the scope of thisinvention.

The hard segments of the polymer can be formed by a reaction between thediisocyanate or multifunctional isocyanate and chain extender. Someexamples of suitable isocyanates for preparation of the hard segment ofthis invention include aromatic diisocyanates and their polymeric formor mixtures of isomers or combinations thereof, such as toluenediisocyanates, naphthalene diisocyanates, phenylene diisocyanates,xylylene diisocyanates, and diphenylmethane diisocyanates, and otheraromatic polyisocyanates known in the art. Other examples of suitablepolyisocyanates for preparation of the hard segment of this inventioninclude aliphatic and cycloaliphatic isocyanates and their polymers ormixtures or combinations thereof, such as cyclohexane diisocyanates,cyclohexyl-bis methylene diisocyanates, isophorone diisocyanates andhexamethylene diisocyanates and other aliphatic polyisocyanates.Combinations of aromatic and aliphatic or arylakyl diisocyanates canalso be used.

The isocyanate component can be provided in any suitable form, examplesof which include 2,4′-diphenylmethane diisocyanate, 4,4′-diphenylmethanediisocyanate, and mixtures or combinations of these isomers, optionallytogether with small quantities of 2,2′-diphenylmethane diisocyanate(typical of commercially available diphenylmethane diisocyanates). Otherexamples include aromatic polyisocyanates and their mixtures orcombinations, such as are derived from phosgenation of the condensationproduct of aniline and formaldehyde. It is suitable to use an isocyanatethat has low volatility, such as diphenylmethane diisocyanate, ratherthan more volatile materials such as toluene diisocyanate. An example ofa particularly suitable isocyanate component is the 4,4′-diphenylmethanediisocyanate (“MDI”). Alternatively, it can be provided in liquid formas a combination of 2,2′-, 2,4′- and 4,4′-isomers of MDI. In a preferredembodiment, the isocyanate is MDI and even more preferably4,4′-diphenylmethane diisocyanate.

Some examples of chain extenders for preparation of the hard segment ofthis invention include, but are not limited, to short chain diols ortriols and their mixtures or combinations thereof, such as 1,4-butanediol, 2-methyl-1,3-propane diol, 1,3-propane-diol ethylene glycol,diethylene glycol, glycerol, cyclohexane dimethanol, triethanol amine,and methyldiethanol amine. Other examples of chain extenders forpreparation of the hard segment of this invention include, but are notlimited to, short chain diamines and their mixtures or combinationsthereof, such as dianiline, toluene diamine, cyclohexyl diamine, andother short chain diamines known in the art.

The soft segment consists of urethane terminated polyol moieties, whichare formed by a reaction between the polyisocyanate or diisocyanate orpolymeric diisocyanate and polyol. Examples of suitable diisocyanatesare denoted above. Some examples of polyols for preparation of the softsegment of this invention include but are not limited to polyalkyleneoxide ethers derived form the condensation of alkylene oxides (e.g.ethylene oxide, propylene oxide, and blends thereof), as well astetrahyrofuran based polytetramethylene ether glycols, polycaprolactonediols, polycarbonate diols and polyester diols and combinations thereof.In a preferred embodiment, the polyols are polytetrahydrofuran polyols(“PTHF”), also known as polytetramethylene oxide (“PTMO”) orpolytetramethylene ether glycols (“PTMEG”). Even more preferably, theuse of two or more of PTMO diols with different molecular weightsselected from the commercially available group consisting of 250,650,1000, 1400, 1800, 2000 and 2900.

Two or more PTMO diols of different molecular weight can be used as ablend or separately, and in an independent fashion as between thedifferent parts of the two part system. The solidificationtemperature(s) of PTMO diols is generally proportional to theirmolecular weights. The compatibility of the PTMO diols with such chainextenders as 1,4-butanediol is generally in the reverse proportion tomolecular weight of the diol(s). Therefore the incorporation of the lowmolecular weight PTMO diols in the “curative” (part B) component, andhigher molecular weight PTMO diols in the prepolymer (part A) component,can provide a two-part system that can be used at relatively lowtemperature. In turn, good compatibility of the low molecular weightPTMO diols with such chain extenders as 1,4-butanediol permits thepreparation of two part systems with higher (prepolymer to curative)volume ratio. Amine terminated polyethers and/or polycarbonate-baseddiols can also be used for building of the soft segment.

The PU can be chemically crosslinked, e.g., by the addition ofmultifunctional or branched OH-terminated crosslinking agents or chainextenders, or multifunctional isocyanates. Some examples of suitablecrosslinking agents include, but are not limited to, trimethylol propane(“TMP”), glycerol, hydroxyl terminated polybutadienes, hydroxylterminated polybutadienes (HOPB), trimer alcohols, Castor oilpolyethyleneoxide (PEO), polypropyleneoxide (PPO) and PEO-PPO triols. Ina preferred embodiment, HOPB is used as the crosslinking agent.

This chemical crosslinking augments the physical or “virtual”crosslinking of the polymer by hard segment domains that are in theglassy state at the temperature of the application. The optimal level ofchemical cross-linking improves the compression set of the material,reduces the amount of the extractable components, and improves thebiodurability of the PU. This can be particularly useful in relativelysoft polyurethanes, such as those suitable for the repair of damagedcartilage. Reinforcement by virtual cross-links alone may not generatesufficient strength for in vivo performance in certain applications.Additional cross-linking from the soft segment, potentially generated bythe use of higher functional polyols can be used to provide stiffer andless elastomeric materials. In this manner a balancing of hard and softsegments, and their relative contributions to overall properties can beachieved.

Additionally, a polymer system of the present invention preferablycontains at least one or more, biocompatible catalysts that can assistin controlling the curing process, including the following periods: (1)the induction period, and (2) the curing period of the biomaterial.Together these two periods, including their absolute and relativelengths, and the rate of acceleration or cure within each period,determines the cure kinetics or profile for the composition. Someexamples of suitable catalysts for preparation of the formed PU of thisinvention include, but are not limited to, tin and tertiary aminecompounds or combinations thereof such as dibutyl tin dilaurate, and tinor mixed tin catalysts including those available under the tradenames“Cotin 222”, “Formrez UL-22” (Witco), “dabco” (a triethylene diaminefrom Sigma-Aldrich), stannous octanoate, trimethyl amine, and triethylamine. In a preferred embodiment, the catalyst is Formrez UL-22 (Witco).In an alternative preferred embodiment, the catalyst is a combinationCotin 222 (CasChem) and dabco (Sigma-Aldrich).

The in vivo and ex vivo cured polyurethanes of this invention can beformed by the reaction of two parts. Part I of which (alternativelyreferred to as Part A) includes a di- or multifunctional isocyanate orquasi-prepolymer which is the reaction product of one or moreOH-terminated components, and one or more isocyanates. Part II of thepolyurethane (alternatively referred to as Part B herein) is a curativecomponent that includes of one or more chain extenders and one or morepolyols, and one or more catalysts, and other additives such asantioxidants and dyes. For a suitable formed PU, the stoichiometrybetween Parts I (quasiprepolymer) and II (curative component), expressedin terms of NCO:OH molar ratio of the isocyanate terminated pre-polymer(Part I) and the curative component (Part II) is preferably within therange of about 0.8 to 1.0 to 1.2 to 1.0, and more preferably from about0.9 to 1 to about 1.1 to 1.0.

Optionally, a reactive polymer additive can be included and is selectedfrom the group consisting of hydroxyl- or amine-terminated compoundsselected from the group consisting of poybutadiene, polyisoprene,polyisobutylene, silicones, polyethylene-propylenediene, copolymers ofbutadiene with acryolnitrile, copolymers of butadiene with styrene,copolymers of isoprene with acrylonitrile, copolymers of isoprene withstyrene, and mixtures of the above.

Suitable compositions for use in the present invention are thosepolymeric materials that provide an optimal combination of propertiesrelating to their manufacture, application, and in vivo use. In theuncured state, such properties include component miscibility orcompatibility, processability, and the ability to be adequatelysterilized or aseptically processed and stored. In the course ofapplying such compositions, suitable materials exhibit an optimalcombination of such properties as flowability, moldability, and in vivocurability. In the cured state, suitable compositions exhibit an optimalcombination of such properties as strength (e.g., tensile andcompressive), modulus, biocompatibility and biostability.

When cured, the compositions demonstrate an optimal combination ofproperties, particularly in terms of their conformational stability andretention of physical shape, dissolution stability, biocompatibility,and physical performance, as well mechanical properties such asload-bearing strength, tensile strength, shear strength, shear fatigueresistance, impact absorption, wear resistance, and surface abrasionresistance. Such performance can be evaluated using procedures commonlyaccepted for the evaluation of natural tissue and joints, as well as theevaluation of materials and polymers in general. In particular, apreferred composition, in its cured form, exhibits mechanical propertiesthat approximate or exceed those of the natural tissue it is intended toprovide or replace.

To achieve these desirable uncured and delivery properties, a “polymersystem”, as used herein refers to the component or components used toprepare a polymeric composition of the present invention. In a preferredembodiment, a polymer system comprises the components necessary to formtwo parts: Part I being an NCO terminated pre-polymer (optionallyreferred to as an “isocyanate quasi-polymer”). The quasi-polymer of PartI typically includes a polyol component, optionally in combination witha hydrophobic additive component, and an excess of an isocyanatecomponent. Part II of the two component system can include onelong-chain polyols, chain extenders and/or cross-linkers, together withother ingredients (e.g., catalysts, stabilizers, plasticizers,antioxidants, dyes and the like). Such adjuvants or ingredients can beadded to or combined with any other component thereof either prior to orat the time of mixing, delivery, and/or curing.

In a particularly preferred embodiment, a polymer system of thisinvention is provided as a plurality of component parts and employs oneor more catalysts. The component parts, including catalyst, can be mixedto initiate cure, and then delivered, set and fully cured underconditions (e.g., time and exotherm) sufficient for its desired purpose.Upon the completion of cure, the resultant composition provides anoptimal combination of properties for use in repairing or replacinginjured or damaged tissue. In a particularly preferred embodiment, theformulation provides an optimal combination of such properties ascompatibility and stability of the biomaterial parts, ex vivo or in situcure capability and characteristics (e.g., extractable levels,biocompatibility, thermal/mechanical properties), mechanical properties(e.g., tensile, tear and fatigue properties), and biostability.

The volume ratio of the parts can also be used to improve and affect theuncured and curing properties Compositions having two or more parts, arepreferred. Where two parts are used, the relative volumes can range, forinstance, from 1:10 to 10:1 (quasi-prepolymer to curative components,based on volume). A presently preferred range is between 2:1 and 1:2. Asthose skilled in the art will appreciate, given the present description,the optimal volume ratio is largely determined by the compatibility andthe stability of part A and B.

In choosing an optimal volume ratio for a given formulation, thoseskilled in the art, given the present description, will appreciate themanner in which the following considerations can be addressed. Theviscosity of the reactive parts, at the temperature used for eitherinjection-molding preformed components, or for in situ cure, shouldprovide an acceptable degree of mixing and flow rate, without causingmechanical failure of any component of the delivery system includingcartridge, static mixer, gun and other components.

Preferably, the biomaterial is sufficiently flowable to permit it to bedelivered (e.g., injected) into the mold or tissue site. The compositionof both reactive parts must be such that these parts are homogeneous andphase stable in the temperature range of the application. Generally, themaximum temperature of the reaction exotherm is proportional to theconcentration of the reactive groups in the mixed polymer. A highconcentration of the reactive groups might evolve too high reactionexothermal energy and therefore cause thermal damage to the surroundingtissues. The reactive parts will preferably remain substantially liquidin form during mixing.

A desired and stable volume ratio of the components can be achieved inany suitable manner, e.g., by the use of dual-compartment cartridgeswith constant volume ratio or by using the injectors with delivery ratesindependently variable for each component.

Compatibility of the composition can also be affected (and improved) inother ways as well, e.g., by pre-heating the components prior to polymerapplication. To enhance the homogeneity of the components, thecomponents of a preferred composition of this invention are preferablypreheated before mixing and delivery, e.g., by heating to about 40 C,more preferably about 60 C, to about 80 C for about 2 to about 6 hoursprior to use or for the time necessary for complete melting and formingof the member. Preferably, the composition parts are cooled back toabout 35 C to 37 C before use in injection.

Fully cured polymeric (e.g., polyurethane) biomaterials suitable for usein forming components of this invention provide an optimal combinationof such properties as creep and abrasion resistance. Preferably, forinstance, the biomaterial provides DIN abrasion values of less thanabout 100 mm³, more preferably less than about 80 mm³ and mostpreferably less than about 60 mm³, as determined by ASTM Test MethodD5963-96 (“Standard Test Method for Rubber Property Abrasion ResistanceRotary Drum Abrader”).

What is claimed is:
 1. A system for the creation or modification of anorthopedic joint within a mammalian body, the system comprising one ormore partially or fully preformed polymeric components forming a kneeimplant that provides a first major surface adapted to be positionedupon and congruent with the tibial surface of the knee, and a secondmajor surface adapted to be positioned against the femoral condyle ofthe knee, and wherein the second major surface is provided with afemoral glide path to facilitate its performance in situ, the glide pathbeing in the form of a generally central depression, the implant furthercomprising one or more tibial projections adapted to extend distallyover a rim of a tibial plateau in order to improve fixation in situ. 2.A system according to claim 1 wherein the polymeric components areprovided in the form of a single preformed component comprising abiomaterial partially or completely cured in an ex vivo mold.
 3. Asystem according to claim 2 wherein the component is preformed in a moldhaving an anterior planar cup edge that is substantially perpendicularto the plane of the cup itself, and a mesial edge that is tapered toaccommodate the corresponding shape of a human tibial spine.
 4. A systemaccording to claim 3 wherein the mold is adapted to permit control ofsizing, conformance to the joint site, implant thickness and angularcorrection.
 5. A system according to claim 1 wherein one or more of thepolymeric components comprise a polyurethane.
 6. A system according toclaim 5 wherein the polyurethane is prepared from polyisocyanate(s),short and long chain polyols, and including one or more ingredientsselected from the group hydrophobic additive(s), tin or aminecatalyst(s), or both, and antioxidant(s).
 7. A system according to claim6 wherein the hydrophobic additive comprises hydroxyl-terminatedpolybutadiene, and the tin or amine catalyst(s), or both, are adapted topreferentially promote isocyanate-hydroxyl reaction mechanisms and areselected from the group consisting of UL22, Cotin 222,1,4-diazabicyclo[2.2.2]octane (dabco), and dibutyltin dilaurate (DBTDL),and combinations thereof.
 8. A system according to claim 5 wherein thepolyurethane comprises aromatic polyisocyanates, PTMO's, and short chaindiols.
 9. A system according to claim 5 wherein the polyurethanecomprises an isocyanate selected from the group consisting of aromatic,aliphatic and arylakyl diisocyanates, and combinations thereof.
 10. Asystem according to claim 9 wherein the isocyanate is selected from thegroup consisting of toluene diisocyanates, naphthalene diisocyanates,phenylene diisocyanates, xylylene diisocyanates, diphenylmethanediisocyanates, cyclohexane diisocyanates, cyclohexyl-bis methylenediisocyanates, isophorone diisocyanates and hexamethylene diisocyanate.11. A system according to claim 10 wherein the glide path is in the formof a generally central depression about 0.5 mm to about 5 mm deep at itslowest point and about 20 mm to about 50 mm in length by 10 mm to 30 mmin width.
 12. A system according to claim 1 wherein the glide path is inthe form of a generally central oval depression about 0.5 mm to about 5mm deep at its lowest point and about 20 mm to about 50 mm in length by10 mm to 30 mm in width.
 13. A system according to claim 1 wherein thetibial projection(s) are adapted to catch the posterior portion of thetibial plateau by extending over the rim of the tibial plateau distally,and the preformed component has dimensions on the order of between about31 to about 60 mm in the anterior-posterior dimension, between about 20mm to about 40 mm in the medial-lateral dimension, and a maximumthickness, at the posterior lip, of between about 8 mm and about 20 mm,or about 3 mm to about 10 mm greater than the thickness of the implantat the center.
 14. A system according to claim 13 wherein the surface ofthe polymeric component is provided or modified with reactive groups topromote tissue adhesion.
 15. A system according to claim 13 wherein theglide path is in the form of a generally central oval depression about0.5 mm to about 5 mm deep at its lowest point and about 20 mm to about50 mm in length by 10 mm to 30 mm in width.